The proposed studies will address the hypothesis that gp35 a 33-40 kD glycoprotein is a signal-transducing molecule that interacts with ligand-binding structures in order to regulate the cellular responses of NK cells and T cells. The specific aims are: 1) to determine whether gp35 MAb are mitogenic for freshly isolated NK cells, affect the cytolytic activity of NK cells, and activate NK cells to produce cytokines; 2) to determine whether there are cell-surface molecules which are physically associated with gp35 on NK cells and T cells; 3) to determine, by generating gp35-loss mutants of RNK-16, whether gp35 is required for target cell-induced PPI turnover within RNK-16, for cytotoxicity, and for CD2-mediated signaling; and 4) to clone the gene that encodes gp35.